Related Experiment Video

Updated: Sep 10, 2025

Preparation of Pseudo-Typed H5 Avian Influenza Viruses with Calcium Phosphate Transfection Method and Measurement of Antibody Neutralizing Activity
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Preparation of Pseudo-Typed H5 Avian Influenza Viruses with Calcium Phosphate Transfection Method and Measurement of Antibody Neutralizing Activity

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Immunopathogenesis of lethal H5N1 avian influenza virus clade 2.3.4.4b infection in macaques

Hanne Andersen1, Malika Aid2, Jonathan J Stone3

  • 1Bioqual, Inc., Rockville, MD 20850, USA.

Immunity
|August 19, 2025
PubMed

Insights

The H5N1 avian influenza virus (H5N1) outbreak poses a pandemic threat. This study reveals that inflammation and immune dysregulation drive severe H5N1 disease pathogenesis in nonhuman primates.

Area of Science:

  • Virology
  • Immunology
  • Pathogenesis

Background:

  • The H5N1 avian influenza virus clade 2.3.4.4b outbreak is a significant pandemic concern.
  • Understanding the pathogenesis of severe H5N1 disease after respiratory infection is crucial.

Purpose of the Study:

  • To investigate the mechanisms of severe H5N1 disease pathogenesis in nonhuman primates.
  • To analyze the host response to H5N1 infection using multi-omics.

Main Methods:

  • Infection of cynomolgus and rhesus macaques with the H5N1 isolate A/Texas/37/2024 (huTX37-H5N1).
  • Clinical monitoring, mortality assessment, and multi-omics analysis (including cytokine, immune cell, complement, coagulation, apoptosis, and immune exhaustion pathways).

Main Results:

  • Cynomolgus macaques experienced 100% lethal pneumonia within 7 days.
  • Rhesus macaques showed dose-dependent mortality, with survivors developing protective immunity.
  • Multi-omics revealed robust induction of inflammation, innate immunity, complement, coagulation, apoptosis, and immune exhaustion.

Conclusions:

  • Inflammation and immune dysregulation are key drivers of H5N1 pathogenesis in nonhuman primates.
  • Nonhuman primates serve as a relevant model for studying severe H5N1 disease.
Keywords:
H5N1immunityinfluenzamacaquepathogenesis

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